Martin Sipkoff
MANAGED CARE April 2010. ©MediMedia USA

Sometimes the cure can pose the biggest threat, the data suggest

In the past decade, medication safety has received increased attention from practitioners and health plans. “We believe medication safety is a top priority,” says Edmund Pezalla, MD, chief clinical officer at Aetna Pharmacy Management, “and place an emphasis on providing whatever information we can to our providers about the importance of reducing errors.”

In an attempt to help practitioners and plans gather and to disseminate information about drug-induced diseases — defined as adverse medical reactions either induced or exacerbated by drugs prescribed to treat a medical problem — the American Society of Health-System Pharmacists (ASHP) recently published its second edition of Drug-Induced Diseases: Prevention, Detection, and Management.

“This is an under-recognized problem,” says James Tisdale, PharmD, a professor at the School of Pharmacy & Pharmaceutical Sciences at Indiana University in Indianapolis and co-editor of the manual. “No good estimate exists on the overall cost of drug-induced illness, but research demonstrates that between 5 percent and 17 percent of all hospital admissions are caused by adverse reactions to prescribed medications.”

The lack of clear data on the mortality and morbidity of drug-induced diseases (DID) — and related costs — is in itself a problem, says another co-editor, Douglas Miller, PharmD, professor in the department of pharmacy practice in the College of Pharmacy and Health Science at Wayne State University in Detroit.

“The proper role for managed care in the management of DIDs is enhanced awareness and education,” says Miller. “Health plans and pharmacy benefit management companies can play an important role in heightening awareness that drugs can actually cause diseases. This is an educational process that plans and PBMs can implement or improve upon through the dissemination of information. It is not the kind of problem that could be successfully managed through formulary control because people need drugs. It can only be managed when practitioners have the kind of information necessary to recognize an adverse drug reaction from a prescribed medication when it occurs.”

That is what the ASHP manual is designed to accomplish, says Tisdale. It is similar in purpose to the DSM-IV manual for mental illness. The first edition was published five years ago, and was viewed by practitioners as filling an informational void on the symptomology of DIDs, say the editors. “Doctors simply are not trained to look for adverse drug reactions as the cause of a disease,” he says. “Awareness of symptomology is a key first step.”

The manual is designed to provide plans, PBMs, and especially practitioners with critical data about what drugs can cause what specific disease. It is divided into sections addressing dermatologic, neurologic, psychiatric, pulmonary, cardiovascular, endocrine, gastrointestinal, kidney, and hematological DIDs, as well as drug-caused bone, joint, and muscle disorders.

Awareness of symptoms

Awareness of symptoms is critical to reducing DIDs, say the authors, and so are efforts through medication histories — efforts that health plans can encourage through communication with primary care physicians. Miller and Tisdale co-wrote a chapter titled “Evaluating Patients for Drug-Induced Diseases.” They list several improvements to current medication history methodologies, and encourage plans to help educate primary care doctors about including such efforts as standard protocols:

  • Reviews of patient histories and charts before medication histories are gathered in order to enhance efficiency
  • Privacy and patience in the gathering of information
  • A nonjudgmental attitude
  • Questioning whether other physicians are prescribing additional medications
  • Communication with a patient’s community pharmacist to determine adherence

Since the first edition, several drugs have been removed from the market through a combination of private reporting and governmental intervention. According to the editors, examples include pemoline (hepatotoxicity), pergolide (heart value damage), and tegasarod (stroke and myocardial infarction). “These events occurred despite efforts beforehand to make certain the drugs were safe,” says Miller. “Not all adverse drug events or associated DIDs are documented ... or even made known to the FDA.”

The authors encourage the use of the Naranjo scale, developed nearly 30 years ago to determine the probability of adverse drug events. It lists a series of questions and assigns a point scale to the answers, measuring the probability of an adverse drug event (including DIDs) by total point count. “This is a very valuable but underutilized tool,” says Miller.

The editors are convinced that the problem of DIDs is growing worse as more and more drugs come on the market and as our population ages, says Miller. “We encourage a heightening effort to report adverse drug events, including the subset of events that are drug-induced,” he says. “Claims data could be invaluable in such an effort, especially if plans and PBMs were to take the initiative.” More information is available at

Scale underutilized for determining probability of adverse drug events

Published in 1981 in the journal Clinical Pharmacology & Therapeutics in an article by researchers from the University of Toronto, and now in the public domain, the Naranjo scale is an underutilized tool for determining whether disease symptoms are caused by drugs, according to authors of a recent manual on drug-induced disease published by the American Society of Health-System Pharmacists.

Naranjo scale for estimating the probability of adverse drug events
Question Points
Are there previous conclusive reports on this reaction? Yes (+1) No (0) Don’t know (0)
Did the adverse event appear after the suspected drug was administered? Yes (+2) No (–1) Don’t know (0)
Did the adverse reaction improve when the drug was discontinued or a specific antagonist was administered? Yes (+1) No (0) Don’t know (0)
Did the adverse reaction reappear when the drug was readministered? Yes (+2) No (–1) Don’t know (0)
Are there alternative causes (other than the drug) that could on their own have caused the reaction? Yes (–1) No (+2) Don’t know (0)
Did the reaction reappear when a placebo was given? Yes (–1) No (+1) Don’t know (0)
Was the drug detected in the blood (or other fluids) in concentrations known to be toxic? Yes (+1) No (0) Don’t know (0)
Was the reaction more severe when the dose was increased or less severe when dose was decreased? Yes (+1) No (0) Don’t know (0)
Did the patient have a similar reaction to the same or similar drug in any previous exposure? Yes (+1) No (0) Don’t know (0)
Was the adverse event confirmed by any objective evidence? Yes (+1) No (0) Don’t know (0)
Probability that adverse drug event has occurred: Total points
≥9 — highly probable
≥5 — probable
≥1 — possible
0 — doubtful
Source: American Society of Health-System Pharmacists

Contributing editor Martin Sipkoff can be reached at

“Doctors simply are not trained to look for adverse drug reactions as the cause of a disease,” says James Tisdale, PharmD, co-editor of Drug-Induced Diseases: Prevention, Detection, and Management.

Managed Care’s Top Ten Articles of 2016

There’s a lot more going on in health care than mergers (Aetna-Humana, Anthem-Cigna) creating huge players. Hundreds of insurers operate in 50 different states. Self-insured employers, ACA public exchanges, Medicare Advantage, and Medicaid managed care plans crowd an increasingly complex market.

Major health care players are determined to make health information exchanges (HIEs) work. The push toward value-based payment alone almost guarantees that HIEs will be tweaked, poked, prodded, and overhauled until they deliver on their promise. The goal: straight talk from and among tech systems.

They bring a different mindset. They’re willing to work in teams and focus on the sort of evidence-based medicine that can guide health care’s transformation into a system based on value. One question: How well will this new generation of data-driven MDs deal with patients?

The surge of new MS treatments have been for the relapsing-remitting form of the disease. There’s hope for sufferers of a different form of MS. By homing in on CD20-positive B cells, ocrelizumab is able to knock them out and other aberrant B cells circulating in the bloodstream.

A flood of tests have insurers ramping up prior authorization and utilization review. Information overload is a problem. As doctors struggle to keep up, health plans need to get ahead of the development of the technology in order to successfully manage genetic testing appropriately.

Having the data is one thing. Knowing how to use it is another. Applying its computational power to the data, a company called RowdMap puts providers into high-, medium-, and low-value buckets compared with peers in their markets, using specific benchmarks to show why outliers differ from the norm.
Competition among manufacturers, industry consolidation, and capitalization on me-too drugs are cranking up generic and branded drug prices. This increase has compelled PBMs, health plan sponsors, and retail pharmacies to find novel ways to turn a profit, often at the expense of the consumer.
The development of recombinant DNA and other technologies has added a new dimension to care. These medications have revolutionized the treatment of rheumatoid arthritis and many of the other 80 or so autoimmune diseases. But they can be budget busters and have a tricky side effect profile.

Shelley Slade
Vogel, Slade & Goldstein

Hub programs have emerged as a profitable new line of business in the sales and distribution side of the pharmaceutical industry that has got more than its fair share of wheeling and dealing. But they spell trouble if they spark collusion, threaten patients, or waste federal dollars.

More companies are self-insuring—and it’s not just large employers that are striking out on their own. The percentage of employers who fully self-insure increased by 44% in 1999 to 63% in 2015. Self-insurance may give employers more control over benefit packages, and stop-loss protects them against uncapped liability.